Sex differences in the functional connectivity of the amygdalae in association with cortisol

Abstract

Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal-occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required.

Multimodal evaluation of the amygdala's functional connectivity

“…In addition, whilst sex was included as a covariate of no interest in the rs-fmri analyses, we did not have sufficient information (e.g., menstrual cycle phase, hormone levels) to thoroughly test for sexual dimorphism effects in our rs-fmri analyses. Indeed, sex differences in rs-fmri amygdala connectivity with brain regions including the IFG as well as different regulatory effects of cortisol on amygdala connectivity have been reported in healthy adults (Kogler et al 2016). Finally, like many previous studies, we used conventional methods for our rs-fmri connectivity analysis.…”

Imaging structural and functional brain development in early childhood

“…In adults, sex differences in amygdala functional connectivity have been reported with females showing stronger positive connectivity between the amygdala and areas associated with face monitoring and discrimination (middle temporal gyrus and inferior frontal gyrus), sensory processing (postcentral gyrus), and emotional processing (hippocampus) and males showing greater connectivity between the amygdala and areas involved in the acquisition of conditioned fear, extinction learning and extinction memory 139, 140 , consistent with observations during later childhood and adolescent development 141 .…”

Sex Differences in Trauma-Related Psychopathology: a Critical Review of Neuroimaging Literature (2014–2017)

“…Females showed stronger rs-FC than males between the left amygdala and prefrontal regions, as well as hippocampus, and an interaction of sex and cortisol appeared: In females, cortisol was negatively associated with connectivity of the amygdala with areas including striatal regions (involved in motivation and reward experience) and prefrontal regions. Contrarily in males, positive associations of cortisol with rs-FC of the left amygdala and these structures were observed [106]. Thus, fronto-limbic emotional regulation may have a reversed relationship with cortisol among males and females.…”